@article{1ddaddc090524a9a9e7050c386c5c117,
title = "LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration",
abstract = "Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.",
author = "Mi Deng and Xun Gui and Jaehyup Kim and Li Xie and Weina Chen and Zunling Li and Licai He and Yuanzhi Chen and Heyu Chen and Weiguang Luo and Zhigang Lu and Jingjing Xie and Hywyn Churchill and Yixiang Xu and Zhan Zhou and Guojin Wu and Chenyi Yu and Samuel John and Kouyuki Hirayasu and Nam Nguyen and Xiaoye Liu and Fangfang Huang and Leike Li and Hui Deng and Haidong Tang and Sadek, {Ali H.} and Lingbo Zhang and Tao Huang and Yizhou Zou and Benjamin Chen and Hong Zhu and Hisashi Arase and Ningshao Xia and Youxing Jiang and Robert Collins and You, {M. James} and Jade Homsi and Nisha Unni and Cheryl Lewis and Chen, {Guo Qiang} and Fu, {Yang Xin} and Liao, {X. Charlene} and Zhiqiang An and Junke Zheng and Ningyan Zhang and Chengcheng Zhang",
note = "Funding Information: Acknowledgements We thank the National Cancer Institute (1R01CA172268 and 5P30CA142543), the Leukemia & Lymphoma Society (1024-14 and TRP-6024-14), the March of Dimes Foundation (1-FY14-201), the Cancer Prevention and Research Institute of Texas (RP140402, DP150056, RP180435, PR150551, and RR150072), the Robert A. Welch Foundation (I-1834 and AU-0042-20030616), the National Natural Science Foundation of China (81570093, 81422001, and 81721004), the National Basic Research Program of China (2014CB965000), and the China Scholarship Council (201608330307) for support. We also thank G. Salazar for editing the manuscript and Y. Dang for RStudio coding. Publisher Copyright: {\textcopyright} 2018, Springer Nature Limited.",
year = "2018",
month = oct,
day = "25",
doi = "10.1038/s41586-018-0615-z",
language = "English (US)",
volume = "562",
pages = "605--609",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7728",
}